title: Identification of AP2S1 mutation and effects of low calcium formula in an infant with hypercalcemia and hypercalciuria.
abstract: BACKGROUND
  Although AP2S1 has recently been shown to be a causative gene for familial hypocalciuric hypercalcemia type 3 (FHH3), knowledge about FHH3 remains poor.
  
  
  OBJECTIVE
  Our objective was to report AP2S1 mutation and effects of low calcium formula in a patient with hypercalcemia and hypercalciuria.
  
  
  METHODS
  This Japanese female infant was found to have hypercalcemia by a routine laboratory test for poor weight gain on breast feeding. At 49 days of age, serum calcium (adjusted by Payne's formula) was 13.1 mg/dL, intact PTH 27 pg/mL, and urinary calcium-to-creatinine ratio 1.29 mg/mg. There was no evidence for hyperparathyroidism, PTHrP-producing neoplasm, and vitamin D excess. These data, except for hypercalciuria, appeared to be consistent with defective calcium-sensing receptor-mediated signaling. With use of low calcium formula containing 2.6 mg/dL of calcium, she showed catch-up growth, and serum calcium was decreased, as was urinary calcium-to-creatinine ratio. Furthermore, feeding with a mixture of low calcium formula and standard formula with a 2:1 ratio maintained serum calcium ∼12 mg/dL without markedly increasing serum PTH.
  
  
  RESULTS
  Although no pathologic mutation was detected in CASR or GNA11, a presumably de novo heterozygous mutation (p.Arg15Leu), a previously reported causative mutation for FHH3, was identified in AP2S1 of this patient.
  
  
  CONCLUSIONS
  The results imply that lack of hypocalciuria does not necessarily argue against the presence of AP2S1 mutations. The early infantile age of this patient would have played a certain role in the occurrence of hypercalciuria, and low calcium formula is worth attempting in infants with FHH.
authors.affiliation: Department of Pediatrics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. yasuko@hama-med.ac.jp.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Rie
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Eiichirou
authors.initials: E
authors.lastname: Satake
authors.forename: Konosuke
authors.initials: K
authors.lastname: Ohtaka
authors.forename: Toshiki
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000235:genetics*; D034002:Adaptor Protein Complex sigma Subunits / Q000235:genetics*; D019943:Amino Acid Substitution; D002136:Calcium, Dietary; D000075202:Contraindications; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000178:diet therapy / Q000209:etiology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control* / Q000652:urine; D007223:Infant; D041943:Infant Formula; D009154:Mutation; D016896:Treatment Outcome
chemical_list: C510065:AP2S1 protein, human; D033962:Adaptor Protein Complex 2; D034002:Adaptor Protein Complex sigma Subunits; D002136:Calcium, Dietary